The objectives of this research are: (1) The cultivation of M. leprae in tissue culture. Toward this goal we have developed 14 cell strains from tissues of the nine-banded armadillo. This animal, after inoculation with M. leprae, may develop a fatal fulminating disease, more massive than that seen in human lepromatous leprosy. The armadillo has also been reported to develop a spontaneous leprosy-like disease not unlike that caused by inoculation of M. leprae. Therefore, its tissues would appear to be the best candidates to support replication of M.leprae in vitro. Tissues of athymic mice, which are also highly susceptible to M. leprae infection, are also under cultivation and will be investigated for their ability to support growth of M. leprae. We also plan to study, by electron microscopy, the morphology of phagocytized M. leprae in tissue culture to determine if we can correlate morphology with viability as determined by ability of the organisms to replicate in mouse foot pads. (2) The further investigation of neonatally thymectomized Lewis rats (NTLR) as models of human leprosy for the development of chemotherapeutic regimens as well as models of microbial persistence in patients with multibacillary leprosy. We intend to exploit the NTLR in at least two ways. First, the variation, with regimens, of the proportions of M. leprae that persist, will be studied. Second, the effects of various treatments on the proportion of persisting M. leprae will be examined.